Navigation Links
Nuclear receptors battle it out during metamorphosis in new fruit fly model
Date:10/6/2011

PHILADELPHIAGrowing up just got more complicated. Thomas Jefferson University biochemistry researchers have shown for the first time that the receptor for a major insect molting hormone doesn't activate and repress genes as once thought. In fact, it only activates genes, and it is out-competed by a heme-binding receptor to repress the same genes during the larval to pupal transition in the fruit fly.

For the last 20 years, the nuclear receptor known as EcR/Usp was thought to solely control gene transcription depending on the presence or absence of the hormone ecdysone, respectively. But it appears, researchers found, that E75A, a heme-binding receptor that represses genes, replaces EcR/Usp during metamorphosis when ecdysone is absent.

The findings, which could shed light on new ways to better understand and treat hormone-dependent diseases, such as cancer, were published in the online October 6 issue of Molecular Cell.

"This is the first time we've shown that a steroid hormone receptor and heme-binding nuclear receptor are even interacting with each other," said Danika M. Johnston, Ph.D. "We didn't really think the two were competing against each other to bind to the same sequence of DNA and regulate the same genes."

More specifically, in the absence of ecdysone, both ecdysone receptor subunits localize to the cytoplasm, and the heme-binding nuclear receptor E75A replaces EcR/Usp at common target sequences in several genes. During the larval-pupal transition, a switch from gene activation by EcR/Usp to gene repression by E75A is triggered by a decrease in ecdysone concentration and by direct repression of the EcR gene by E75A.

An important nuance of this system is that the heme-binder E75A is sensitive to the amount of nitric oxide in the cell, and it cannot completely fulfill its repressive potential at high levels of this important molecule. Thus, the uncovered system uses changing amounts of two ligands, a steroid hormone and a gas, to regulate transcription during development.

"These were quite unexpected findings, given the longstanding thoughts of this process," said Dr. Johnston, "but we just didn't have the tools in the past to figure out what was going on mechanistically. We're painting a clearer picture now."

Knowing how nuclear receptors regulate gene expression in animal models can provide useful information in the development of drugs. Today, the molecular targets of roughly 13 percent of U.S. Food and Drug Administration approved drugs are nuclear receptors.

"It's very possible that similar situations exist in the mammalian system. That could ultimately lead to different treatments that regulate hormone levels in hormone-dependent diseases, such as cancer," said Dr. Johnston.


'/>"/>

Contact: Steve Graff
stephen.graff@jefferson.edu
215-955-6300
Thomas Jefferson University
Source:Eurekalert  

Related medicine news :

1. Nuclear physics promises earlier detection of brain tumors with just 1 scan
2. Springer enters into partnership with the Korean Society of Nuclear Medicine
3. ESC supports appropriate use of nuclear imaging technology
4. Urgent Nuclear Stress Test Lab Costs Reductions for Physician Practices in Need
5. H1N1, Biodegradable Plastics and Nuclear Physics Highlight Research Areas Undertaken During Houghton College's Summer Research Institute
6. Applied nuclear physics for biomedicine, nuclear security and basic science
7. UND Acquires ProtectionPlus in Ongoing Effort to Reduce Nuclear Stress Testing Costs for Physicians
8. Bengt Roland Långström receives SNMs 2010 Georg Charles de Hevesy Nuclear Pioneer Award
9. Sung-Cheng (Henry) Huang receives 2010 Benedict Cassen Prize for Research in Nuclear Medicine
10. SNMs 2010 Annual Meeting reveals latest developments in molecular imaging and nuclear medicine
11. NIH renews research program to develop medical countermeasures against radiological, nuclear threats
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Nuclear receptors battle it out during metamorphosis in new fruit fly model
(Date:3/29/2017)... Indianapolis, IN (PRWEB) , ... March 29, 2017 ... ... Benefits Study, this webinar provides insight into the challenges employers face in trying ... the complexity of managing employee benefits programs? Adding to the growing complexity, ...
(Date:3/29/2017)... ... March 29, 2017 , ... Dr. Angela Cotey, a noted general dentist in ... pediatric patients, with or without a referral. Dr. Cotey knows that interceptive orthodontics ... and experience. When patients receive early treatment, they may achieve straight teeth with less ...
(Date:3/29/2017)... ARNOLD, Md., and MINNETONKA, Minn. (PRWEB) , ... ... ... for the development of medical office buildings (MOBs) and other outpatient facilities, and ... research project to look exclusively at those questions, Revista and Healthcare Real Estate ...
(Date:3/29/2017)... MD (PRWEB) , ... March 29, 2017 , ... ... is proud to announce the finalization of the company’s executive management team with prominent ... and leading operations is Curio Wellness’ Chief Operating Officer, Ted Dumbauld , who ...
(Date:3/29/2017)... ... , ... HealthCareMandA.com will host an important webinar — Home Health & Hospice: ... recording of the webinar will also be made available following its live presentation. The ... are still popular targets for healthcare investors. This highly fragmented sector bounced back in ...
Breaking Medicine News(10 mins):
(Date:3/29/2017)... 2017  Designers of primary cell wearable medical and ... 50% and extend battery life with the MAX20310 ultra-low ... (PMIC) from Maxim Integrated Products, Inc. (NASDAQ: ... voltage of just 0.7V for new high-energy density battery ... well as the more common Alkaline battery architecture. With ...
(Date:3/29/2017)... , March 29, 2017  NuVasive, Inc. (NASDAQ: ... transforming spine surgery with minimally disruptive, procedurally-integrated solutions, ... 510(k) clearance of the CoRoent® Small Interbody™ System ... levels in the cervical spine. This marks the ... be used at up to four contiguous levels. ...
(Date:3/29/2017)... Utah , March 29, 2017   ... announced today the appointment of Cynthia L. ... Cyndi will be responsible for leading Dynatronics manufacturing, ... and will report to Dynatronics, CEO Kelvyn ... appointment concludes an extensive search process conducted by ...
Breaking Medicine Technology: